Pfizer has launched the first Phase III trial for PF-08046054, a first-in-class PD-L1-targeting antibody-drug conjugate (ADC), in 680 patients with previously treated PD-L1-positive non-small cell lung cancer (NSCLC). The open-label study compares the ADC against docetaxel chemotherapy with co-primary endpoints of overall survival (OS) and progression-free survival (PFS). Phase I data showed 26.7% objective response rate (ORR) in all comers and 32.0% in PD-L1-positive patients, with median duration of response (DOR) of 7.8 months at 1.5mg/kg dosing.

Safety profiles demonstrated manageable toxicity with peripheral sensory neuropathy (27.2%), nausea (25.0%) and diarrhea (23.9%) as common adverse events. PF-08046054 leads five global PD-L1 ADC candidates in development, followed by Henlius's HLX43 in Phase I. The trial initiation positions Pfizer to potentially establish the first ADC approach to immune checkpoint modulation beyond traditional immunotherapy.

PharmCube's NextBiopharm® database shows that, although Pfizer's project is the most advanced, most of the 26 other PD-1/L1 ADC candidates use a dual-target strategy. Click here to request a free trial for NextBiopharm®.